We reinvestigate the validity of mapping the problem of two onsite interacting particles in a random potential onto an effective random matrix model. To this end we first study numerically how the non-interacting basis is coupled by the interaction. Our results indicate that the typical coupling matrix element decreases significantly faster with increasing single-particle localization length than is assumed in the random matrix model. We further show that even for models where the dependency of the coupling matrix element on the single-particle localization length is correctly described by the corresponding random matrix model its predictions for the localization length can be qualitatively incorrect. These results indicate that the mapping of an interacting random system onto an effective random matrix model is potentially dangerous. We also discuss how Imry's block-scaling picture for two interacting particles is influenced by the above arguments.

Im Rahmen der Arbeit in der damaligen DFG-Forschungsgruppe ¨Scientific Parallel Computing¨ wurde ein hierarchischer paralleler Netzgenerator fuer das Finite-Elemente- Programmpaket SPC-PM CFD unter dem Namen NETGEN69 entwickelt. Als Programmiersprache wurde seinerzeit - wie auch in den FEM-Programmen selbst - FORTRAN benutzt. Im Rahmen des Teilprojektes B2 im Sonderforschungsbereich 393 bestand nunmehr die Aufgabe, den Netzgenerator in ein objektorientiertes Layout zu fassen und in C++zu implementieren. Die Beschreibung von Ein- und Ausgabedaten kann in [3] nachgelesen werden. Die Form der Eingabedaten hat sich aus Kompatibilitaetsgruenden nicht geaendert und wird auch in Zukunft so beibehalten werden. Auch das der Assemblierung und FEM-Rechnung zuge- wandte Interface wurde vorerst nicht geaendert. Ein Wrapper, der fuer die Generierung der erwarteten Ausgabedaten aus den netzgeneratoreigenen Datenbestaenden sorgt, ist derzeit in Planung. Diese Lösung ist freilich nur voruebergehender Natur; sie ermoeglicht es uns, den Netzgenerator innerhalb der FEM-Bibliotheken zu testen.

This paper is devoted to asymptotic estimates for the condition numbers $\kappa(T_n(a))=||T_n(a)|| ||T_n^(-1)(a)||$ of large $n\cross n$ Toeplitz matrices $T_N(a)$ in the case where $\alpha \element L^\infinity$ and $Re \alpha \ge 0$ . We describe several classes of symbols $\alpha$ for which $\kappa(T_n(a))$ increases like $(log n)^\alpha, n^\alpha$ , or even $e^(\alpha n)$ . The consequences of the results for singular values, eigenvalues, and the finite section method are discussed. We also consider Wiener-Hopf integral operators and multidimensional Toeplitz operators.

In der Entwicklung der numerischen Simulation im Laufe der letzten Jahre ist ein deutlicher Trend zur Konsolidierung tu beobachten. Neben der wirtschaftlichen Konsolidierung der Anbieter - letztendlich immer weniger Anbieter, die immer mehr anbieten • gibt es noch die technische Konsolidierung der Softwarelösungen. Das Stichwort ist Integration mit der Motivation, verschiedene Solver-Disziplinen unter einem gemeinsamen Dach zu vereinigen. Der Nutzer soll wenn möglich nur noch ein Tool benutzen, das alles kann. Das ist ein ambitioniertes Ziel und technisch in nächster Zeit nicht umsetzbar, da die Unterschiede in den Lösungsansåtzen unterschiedliche Datenmodelle verlangen. Daher ist als ObergangsIOsung die Co-Simulation das Mittel der Wahl. Damit sind verschiedene Solver gemeint, die über entsprechende Schnittstellen reibungslos und vor allem ohne Nutzerinteraktion miteinander kommunizieren, um so ihre volle Leistung zu entfalten. Auf diesem Gebiet wurden in den letzten Jahren deutliche Fortschritte erzielt. MSC Software bringt nun die Möglichkeiten technologisch auf ein neues Level. Der Vortrag zeigt den konzeptionellen Ansatz, den MSC verfolgt und schrittweise umsetzt. Gezeigt werden die Vorteile in der Anwendung für den Nutzer, aber auch die Limitationen, derer man sich immer bewusst sein muss. Mit konkreten Beispielen aus der Praxis werden die Vorteile der Co-Simulation untermauert. Der Fokus des Vortrages liegt auf den Möglichkeiten, die sich für dynamische Systeme aus der Co-Simulation ergeben und wie die traditionellen Grenzen der Mehrkörpersimulation überwunden werden können: Zum einen durch Kopplung mit nichtlinearer FEM aber auch mit CFO. Inhaltlich soll der Vortrag bestenfalls den Vorstellungshorizont der Zuhörer erweitern. in jedem Fall aber konkret belegen, wo die Co-Simulation bessere Ergebnisse erzielt als die herkömmliche, auf einen Solver beschränkte Vorgehensweise.

Articular cartilage is a highly specialized, hierarchically organized tissue covering the articular surfaces of diarthrodial joints that absorbs and distributes forces upon mechanical loading and enables low-friction movement between opposing bone ends. Despite a strong resilience towards mechanical stress, once damaged cartilage is generally not regenerated due to a limited repair potential of the residing cells (chondrocytes) and the local absence of vascularized blood vessels and nerves. Eventually, this may lead to osteoarthritis, a chronic degenerative disorder of the synovial joints which has a strongly growing prevalence worldwide. Modern regenerative therapies that aim to rebuild cartilage tissue in vivo and in vitro using chondrocyte- and stem cell-based methods are still not able to produce tissue constructs with desired biomechanical properties and organization for long-term repair. Therefore, cartilage tissue engineering seeks for new ways to solve these problems. In this regard, the application of hydrogel-based scaffolding materials as artificial matrix environments to support the chondrogenesis of embedded cells and the implementation of appropriate biofabrication techniques that help to reconstitute the zonal structure of articular cartilage are considered as promising strategies for sophisticated cartilage regeneration approaches. In this thesis, a modular starPEG-heparin hydrogel platform as cell-instructive hydrogel scaffold was used in combination with a custom-designed 3D inkjet bioprinting method with the intention to develop a printable 3D in vitro culture system that promotes the chondrogenic differentiation of human mesenchymal stromal cells (hMSC) in printed cell-laden hydrogels with layered architectures in order to fabricate cartilage-like tissue constructs with hierarchical organization. Firstly, the successful bioprinting of horizontally and vertically structured, cell-free and -laden hydrogel scaffolds that exhibit layer thicknesses in the range of the superficial zone, the thinnest articular cartilage layer is demonstrated. The long-term integrity of the printed constructs and the cellular functionality of the plotted cells that generally had a high viability after the printing process are shown by a successful PDGF-BB-mediated hMSC migration assay in a printed multilayered hydrogel construct over a culture period of 4 weeks. Secondly, when the established printing procedures were applied for the chondrogenic differentiation of hMSCs, it was found that the printed cell-laden constructs showed a limited potential for in vitro chondrogenesis as indicated by a weaker immunostaining for cartilage-specific markers compared to casted hydrogel controls. In order to increase the post-printing cell density to tackle the limited printable cell concentration which was regarded as the primary reason for the impaired performance of the printed scaffolds, different conditions with varying culture medium and hydrogel compositions were tested to stimulate 3D cell proliferation. However, a significant 3D cell number increase could not be achieved which ultimately resulted in shifting the further focus to casted hMSC-laden starPEG-heparin hydrogels. Thirdly, the chondrogenic differentiation of hMSCs in casted hydrogels proved to be successful which was indicated by a uniform deposition of cartilage-specific ECM molecules comparable with the outcomes of scaffold-free MSC micromass cultures used as reference system. However, the quantitative analysis of biochemical and physical properties of the engineered hydrogel constructs yielded still significant lower values in relation to native articular cartilage tissue. Fourthly, in order to improve these properties and to enhance the chondrogenesis in starPEGheparin hydrogels, a dualistic strategy was followed. In the first part, specific externally supplied stimulatory cues including a triple growth factor supply strategy and macromolecular crowding were applied. As second part, intrinsic properties of the modular hydrogel system such as the crosslinking degree, the enzymatic degradability and the heparin content were systematically and independently altered. It was found that while the external cues showed no supportive benefits for the chondrogenic differentiation, the reduction of the heparin content in the hydrogel proved to be a key trigger that resulted in a significantly increased cartilage-like ECM deposition and gel stiffness of engineered constructs with low and no heparin content. In conclusion, this work yielded important experiences with regards to the application of inkjet bioprinting for hMSC-based cartilage tissue engineering approaches. Furthermore, the obtained data provided valuable insights into the interaction of MSCs and a surrounding hydrogel-based microenvironment that can be used for the further development of chondrosupportive scaffolding materials which may facilitate the fabrication of cartilage-like tissue constructs.

The thesis focuses on investigating and optimizing a bushing script implemented as a tool in MSC ADAMS/Car. The study provides an insight on the representation of a rubber bushing and identify parameters which can be used to define the properties of a bushing in a simulation environment such as ADAMS/Car. The tool being studied here can be used to implement different kind of bushings such as a hydro bushing and a general rubber bushing, but optimization was implemented for the rubber bushing only. With an increasing reliance on Computer Aided Engineering (CAE) tools in the designing process, it is necessary that the vehicle behaviour can be predicted without relying on physical testing. CAE tools reduces the need of prototypes and provides a faster approach to designing vehicles. MSC ADAMS/Car is one such tool, which has been used here to predict the vehicle dynamic behaviour, which will influence the ride, handling and comfort characteristics of the vehicle. Rubber bushings, which have been studied here, have a significant contribution to the overall stiffness of the vehicle and as such, it is imperative that the tool being used here, is accurate and makes the designing process easy. The rubber bushing can be imagined to be a combination of a non-linear elastic spring, a frequency dependent Maxwell component and an amplitude dependent frictional element. In order to ease the design of the bushing properties, a reduced number of input properties are used to calculate the bushing properties internally. While trying to validate the force hysteresis loop obtained through the model with the measured data, it was seen that the accuracy was quite poor for the model when loading it with dynamic loads corresponding to amplitudes of0.2 mm and lower. The quasi-static loading and dynamic loading above 0.2 mm is shown to have a satisfactory accuracy when compared to the measured data.

Mesenchymal stromal cells (MSC) represent a promising treatment option for tendon disorders and joint diseases, primarily osteoarthritis. Since MSC are highly context-sensitive to their microenvironment, their therapeutic efficacy is influenced by their tissue-specific pathologically altered targets. These include not only cellular components, such as resident cells and invading immunocompetent cells, but also components of the tissue-characteristic extracellular matrix. Although numerous in vitro models have already shown potential MSC-related mechanisms of action in tendon and joint diseases, only a limited number reflect the disease-specific microenvironment and allow conclusions about well-directed MSC-based therapies for injured tendon and joint-associated tissues. In both injured tissue types, inflammatory processes play a pivotal pathophysiological role. In this context, MSC-mediated macrophage modulation seems to be an important mode of action across these tissues. Additional target cells of MSC applied in tendon and joint disorders include tenocytes, synoviocytes as well as other invading and resident immune cells. It remains of critical importance whether the context-sensitive interplay between MSC and tissue- and disease-specific targets results in an overall promotion or inhibition of the desired therapeutic effects. This review presents the authors’ viewpoint on disease-related targets of MSC therapeutically applied in tendon and joint diseases, focusing on the equine patient as valid animal model.

In today’s competitive automotive industry, most companies are trying to make their new designs and features implemented in their products to be ahead of their competitors. However, in the preliminary design stage of CEVT vehicles, dynamic simulation consumes excessive amount of time depending on the complexity of the dynamic model and simulation settings. It is beneficial and possible to shorten the simulation time. This thesis focuses on reducing the dynamic simulation time in ADAMS/Car in engine suspensions’ early development stage. Five simulation time reducing methods, i.e., reducing end time in driver control maneuver, stopping similar simulations, converting specific flexible parts to rigid parts, properly increasing the step size and performing simulation for engine suspension subsystem instead of the full vehicle system, were proposed and investigated separately to study their effects on the simulation time and the accuracy of the fatigue damage results of the engine suspension. With the proper combination of the five methods, total dynamic simulation time was effectively reduced to 61% and the variation of fatigue damage results of each engine suspension component was controlled within 30%. Dynamic modelling of an exhaust system is also included in this thesis and it provides referential data for the packaging design of exhaust system. / I dagens konkurrensutsatta bilindustri försöker de flesta företag att göra sina nya mönster och funktioner implementerbara i sina produkter för att vara före sina konkurrenter. I det preliminära konstruktionsstadiet av CEVT-fordon förbrukar dynamisk simulering dock en stor tid beroende på komplexiteten hos den dynamiska modellen och simuleringsinställningarna. Det är fördelaktigt och möjligt att förkorta simuleringstiden. Denna avhandling fokuserar på att minska den dynamiska simuleringstiden i ADAMS / Car i motorupphängningens tidiga utvecklingsstadium. Med hjälp av bakgrundsstudier och erfarenheter från CEVT’s personal provades fem olika sätt att minska simuleringstiden, samtidigt som simuleringsresultatens noggrannhet kontrollerades. Varje metod användes separat i simuleringen för att studera effekten på resultatens noggrannhet. I slutet kombineras alla metoder i simuleringen för att få bästa möjliga simuleringstid utan att förlora noggrannhet. Genom att kombinera de fem metoderna reducerades den totala dynamiska simuleringstiden till 61% och variationen i utmattningsskadans resultat av varje motorupphängningskomponent kontrollerades inom 30%. Dynamisk modellering av ett avgassystem ingår också i denna avhandling, vilket ger referensdata för framtida förpackningsdesign av avgassysteme

Successful translation of multipotent mesenchymal stromal cell (MSC)-based therapies into clinical reality relies on adequate cell production procedures. These should be available not only for human MSC, but also for MSC from animal species relevant to preclinical research and veterinary medicine. The cell culture medium supplementation is one of the critical aspects in MSC production. Therefore, we previously established a scalable protocol for the production of buffy-coat based equine platelet lysate (ePL). This ePL proved to be a suitable alternative to fetal bovine serum (FBS) for equine adipose-derived (AD-) MSC culture so far, as it supported AD-MSC proliferation and basic characteristics. The aim of the current study was to further analyze the functional properties of equine AD-MSC cultured with the same ePL, focusing on cell fitness, genetic stability and pro-angiogenic potency. All experiments were performed with AD-MSC from n = 5 horses, which were cultured either in medium supplemented with 10% FBS, 10% ePL or 2.5% ePL. AD-MSC cultured with 2.5% ePL, which previously showed decreased proliferation potential, displayed higher apoptosis but lower senescence levels as compared to 10% ePL medium (p < 0.05). Non-clonal chromosomal aberrations occurred in 8% of equine AD-MSC cultivated with FBS and only in 4.8% of equine AD-MSC cultivated with 10% ePL. Clonal aberrations in the AD-MSC were neither observed in FBS nor in 10% ePL medium. Analysis of AD-MSC and endothelial cells in an indirect co-culture revealed that the ePL supported the pro-angiogenic effects of AD-MSC. In the 10% ePL group, more vascular endothelial growth factor (VEGF-A) was released and highest VEGF-A concentrations were reached in the presence of ePL and co-cultured cells (p < 0.05). Correspondingly, AD-MSC expressed the VEGF receptor-2 at higher levels in the presence of ePL (p < 0.05). Finally, AD-MSC and 10% ePL together promoted the growth of endothelial cells and induced the formation of vessel-like structures in two of the samples. These data further substantiate that buffy-coat-based ePL is a valuable supplement for equine AD-MSC culture media. The ePL does not only support stable equine AD-MSC characteristics as demonstrated before, but it also enhances their functional properties.

Contexte: La cardiopathie ischémique (IHD) reste une cause majeure de mortalité en Amérique du Nord. La thérapie cellulaire cardiaque (CCT) a émergé comme une thérapie prometteuse pour aider à guérir certaines malades cardiaques. Parmi les cellulaires avec propriétés pluripotentes, les cellules stromales mésenchymateuses (MSC) sont prometteuses. Cependant, plusieurs questions demeurent non résolues et certaines défis empêchent l'application clinique de la CCT se dans l'IHD, tels que le faible taux de rétention cellulaire in situ, le suivi des cellules in vivo post-implantation et post-acheminements et l`apoptose. Ici, le traitement préliminaire des MSC avec des facteurs de croissance et leur couplage avec des nanoparticules (NP) seront étudiés comme des méthodes pour optimiser MSC. Méthodes: Des MSCs provenant du rat (rMSC) et du cochon (pMSC) ont été isolés à partir de moelle osseuse. Les rMSC ont été préconditionnées avec SDF-1a, TSG-6 et PDGF-BB, et ensuite soumises à une hypoxie, une privation de sérum et a un stress oxydatif. Des études de cicatrisation ont également été effectués avec rMSCs préconditionnées. En parallèle, de nouvelles NP ferromagnétiques liées aux silicones ont été synthétisées. Les NPs ont été couplées aux pMSCs suivant leur fonctionnalisation avec l`anticorps, CD44, un antigène de surface du MSC bien connu. Par la suite, les études de biocompatibilité ont été réalisées sur pMSC-NP et en incluant des tests des processus cellulaires tels que la migration, l'adhésion, la prolifération et les propriétés de la différenciation. Résultats: Parmi toutes les cytokines testées, PDGF-BB a démontré la plus grande capacité à améliorer la survie de MSC dans des conditions d'hypoxie, de privation de sérum et en reponse au stress oxydatif. La conjugaison de NP a atténué la migration et la prolifération des pMSCs, mais n`a pas changé leur capacité de différenciation. Enfin, la complexe du MSC-NP est détectable par IRM. Conclusion: Nos données suggèrent que de nouvelles stratégies, telles que traitement préliminaire de PDGF-BB et le couplage des nanoparticules ferromagnétiques, peuvent être considérés comme des avenues prometteuse pour optimiser les MSCs pour la CCT. / Background: Ischemic heart disease (IHD) remains a leading cause of mortality in North America. Cardiac cell therapy (CCT) has emerged as a promising therapy to help heal the damaged heart. Among the various candidates for stem-progenitor cells, Mesenchymal Multipotential Stromal/Stem Cells (MSC) is of great promise. However, there remain unresolved issues and challenges that prevent clinical application of MSC-based CCT in IHD. Among the latter, low cellular retention rate, in vivo cell tracking and post-delivery apoptosis. Here in, growth factor preconditioning and MSC coupling to nanoparticles are investigated as methods to optimize MSC. Methods：Lewis Rat MSC (rMSC) and pig MSC (pMSC) were isolated from bone marrow. Rat MSCs were preconditioned with SDF-1a, TSG-6 and PDGF-BB, and then subjected to hypoxia, serum deprivation and oxidative stress. Wound healing assays were also done with preconditioned rat MSCs. In parallel, novel ferromagnetic silicone core-shell nanoparticles (NP) were synthesized. Pig MSCs were coupled to NPs following functionalization of the NPs with an antibody to a well-recognized MSC surface antigen, CD44. Subsequently, biocompatibility studies were performed on the pMSC-NP complex and included testing of key cellular processes such as migration, adhesion, proliferation and differentiation properties. Results: Of all cytokines used, PDGF-BB showed greatest capacity to improve MSC survival under conditions of hypoxia, serum deprivation and oxidative stress. NP conjugation has mitigated effect on the migration and proliferation of pig MSC, but do not change the differentiation capacity of MSC. Finally, the MSC-NP complex was detectable by MRI. Conclusion: Our data suggest that novel strategies, such as PDGF-BB preconditioning and ferromagnetic nanoparticle coupling, can be considered as promising avenues to optimize MSCs for CCT.